Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. (ucsc.edu)
A hallmark of proteome balance is the ubiquitin-proteasome system (UPS) that degrades roughly 80% of multi-ubiquitinated proteins ( Collins and Goldberg, 2017 ). (elifesciences.org)
Ubiquitin-conjugating enzymes, also known as E2 enzymes and more rarely as ubiquitin-carrier enzymes, perform the second step in the ubiquitination reaction that targets a protein for degradation via the proteasome. (wikipedia.org)
Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. (ucsc.edu)
The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome. (embl-heidelberg.de)
E3 ubiquitinligases are therefore a more specific and effective target for drug development in comparison with general proteasome inhibitors to reduce treatment side effects and increase efficacies ( 1 ). (aacrjournals.org)
The ubiquitin-proteasome pathway is an essential quality control mechanism directing degradation of mislocated, misfolded, and damaged proteins, and, by tempering the expression levels Carnosol of specific signaling proteins, it also exerts a level of control over cell physiology [1]. (scienza-under-18.org)
Poly-ubiquitinated proteins, targeted by E3 ubiquitinligases, can be acknowledged and degraded by the 26S proteasome, a multi-subunit, Carnosol multi-catalytic protease machine [2]. (scienza-under-18.org)
Ubiquitin proteasome system (UPS)-mediated NLR turnover plays a pivotal role in the fine-tuned regulation of immune responses. (ubc.ca)
It is the E3 ligase that is responsible for selecting the target protein for ubiquitination and later for degradation in proteasome in to peptides. (helsinki.fi)
It is constitutively associated with chromatin and is required for normal DNA replication (7 8 Rad17 protein Dabigatran etexilate was reported to be regulated by the ubiquitin-proteasome system (UPS) (9). (healthdisparitiesks.org)
Mechanistically, in lung epithelial cells, escalates the degrees of the deSUMOylase SENP2 in the cytosol by impacting its K48 ubiquitylation and its own subsequent degradation with the ubiquitin proteasome. (idplink.net)
Degradation9
In yeast, the glucose-induced degradation-deficient (GID) E3 ligase selectively degrades superfluous gluconeogenic enzymes. (elifesciences.org)
Particularly in yeast, an organism where gluconeogenesis and glycolytic activity are intermittently coordinated, the multi-subunit GID E3 ligase complex specifically targets the surplus of gluconeogenic enzymes, including the conserved Fructose-1,6-bisphosphatase 1 (Fbp1), for proteasomal degradation. (elifesciences.org)
The E3 molecules responsible for substrate identification and binding are thus the mechanisms of substrate specificity in proteasomal degradation. (wikipedia.org)
Mitogen-activated protein kinase (MAPK) p38 phosphorylates Siah2 under hypoxic conditions, causing it to relocalize to the cytoplasm and subsequently increases its ubiquitin-targeted degradation activity ( 10 ). (aacrjournals.org)
The anaphase-promoting complex (APC) was identified as the ubiquitin E3 ligase that mediates Rad17 degradation (9). (healthdisparitiesks.org)
Hif1 is usually after that targeted for ubiquitin-dependent degradation [5], and Hif1 proteins amounts stay low. (colinsbraincancer.com)
Recently, in addition has been proven to result in the degradation from the SUMO E1 enzyme BET-IN-1 SAE2 to lessen SUMOylation (8). (idplink.net)
Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. (cusabio.com)
Multi-subunit2
The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. (embl-heidelberg.de)
Proteins which contain a RING domain, can either ubiquitinate substrates independently or function as part of a multi-subunit complex. (helsinki.fi)
Proteins12
There are also some proteins which can act as both and E2 and an E3 containing domains which cover both E2 and E3 functionality. (wikipedia.org)
Folding of proteins with WD-repeats: comparison of six members of the WD-repeat superfamily to the G protein beta subunit. (embl.de)
Members of this family include the signal-transducing G protein beta subunit, as well as other proteins that regulate signal transduction, transcription, pre-mRNA splicing, cytoskeletal organization, and vesicular fusion. (embl.de)
This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
E3 ligases consist of a large family of more than 600 proteins ( 3 ), and a few E3 ligases have been classified based on their conserved structural domains (e.g. (bmbreports.org)
Siah proteins, evolutionarily conserved E3 RING zinc finger ubiquitinligases, have recently been implicated in various cancers and show promise as novel anticancer drug targets. (aacrjournals.org)
In chapter 2, by using CRISPR/Cas9 gene editing, genetic analysis and biochemical assays, I identified the differential pairings of typical NLR receptor SOC3 with atypical NLR proteins CHS1 or TN2 to guard the homeostasis of the E3 ligase SAUL1. (ubc.ca)
Moreover, both SUSA proteins are parts of an SCFSUSA2 E3 ligase, forming SCFSUSA2-NLR complex with CHS1-SOC3 or TN2-SOC3 paired NLR proteins. (ubc.ca)
In this study preselected 61 RING type ubiquitin E3 proteins of Arabidopsis thaliana were classified, grouped and analysed to characterize what kind of domains and groups were included. (helsinki.fi)
Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates. (ox.ac.uk)
In the Cul3 ubiquitinligases, Bric-a-brac/Tramtrack/Broad complex (BTB) domain-containing proteins function as a bridge to connect Cul3 and substrates. (tmu.edu.tw)
With the existence of a large number of BTB proteins in human, the Cul3 ubiquitinligases ubiquitinate a wide range of substrates involving in diverse cellular functions. (tmu.edu.tw)
Once a protein has been tagged with one ubiquitin molecule, additional rounds of ubiquitination form a polyubiquitin chain that is recognized by the proteasome's 19S regulatory particle, triggering the ATP-dependent unfolding of the target protein that allows passage into the proteasome's 20S core particle, where proteases degrade the target into short peptide fragments for recycling by the cell. (wikipedia.org)
The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. (ucsc.edu)
Because each of these factors is responsible for the ubiquitination of a subset of the Mtb population, it is likely that additional ubiquitinligases are employed by macrophages to trigger a full xenophagic response during Mtb infection. (bvsalud.org)
Ubiquitination is a reaction cascade, catalyzed by E1 - E2 and finally E3 enzyme which completes the ubiquitination. (helsinki.fi)
In this review, we will discuss recent advances on the functions of Cul3 ubiquitinligases in cancer development, progression, and therapeutic response and the dysregulation of Cul3-mediated ubiquitination events in human malignancies. (tmu.edu.tw)
Enzyme5
A ubiquitin-activating enzyme, or E1, first activates the ubiquitin by covalently attaching the molecule to its active site cysteine residue. (wikipedia.org)
Our findings show that RNF213 represents an undescribed type of a transthiolation E3 enzyme and is regulated by adenine nucleotide concentration via its ATPase core, possibly allowing it to react to changing metabolic conditions in the cell. (biorxiv.org)
The covalent attachment of ubiquitin to a target protein is catalyzed by the sequential action of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). (bmbreports.org)
Enzymatic assays performed with APC purified fromstrains lacking each of the essential subunits revealed that onlycdc27Delta complexes retain detectable activity in the presence of Cdh1.This residual activity depends on the C-box domain of Cdh1, but not on theC-terminal IR domain, suggesting that the C-box mediates a productiveinteraction with an APC subunit other than Cdc27. (embl-heidelberg.de)
Additionally, TCTP has been ascribed a role in DNA damage sensing and restoration, forming complexes with ATM and the DNA binding subunits Ku70 and Ku80 of DNA-dependent protein kinase [16]. (icem2012.org)
In these complexes, the Cullin protein serves as a scaffold to connect two functional modules of the ligases, the catalytic subunit and substrate-binding subunit. (tmu.edu.tw)
Catalytic1
The cryo-EM structure of the trapped RNF213:E2∼Ub intermediate reveals RNF213 C-terminal domain as the E2 docking site, which positions the ubiquitin-loaded E2 proximal to the catalytic zinc finger, facilitating nucleophilic attack of Cys4462 on the E2∼Ub thioester. (biorxiv.org)
Mediates1
Siah mediates its E3 ubiquitin ligase activity by directly binding to its substrates ( 4 ) or by acting as the essential RING domain subunit of a larger E3 complex ( 5 ) and can form homodimers and heterodimers. (aacrjournals.org)
Complex11
Here, we identified all subunits of the mammalian GID/CTLH complex and provide a comprehensive map of its hierarchical organization and step-wise assembly. (elifesciences.org)
Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. (elifesciences.org)
Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1. (ucsc.edu)
The anaphase-promoting complex or cyclosome (APC) is an unusuallycomplicated ubiquitin ligase, composed of 13 core subunits and either oftwo loosely associated regulatory subunits, Cdc20 and Cdh1. (embl-heidelberg.de)
Maize lateral rootless 1 encodes a homolog of the DCAF protein subunit of the CUL4-based E3 ubiquitin ligase complex. (uni-bonn.de)
The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. (novusbio.com)
Rad17 is a subunit of the Rad9-Hus1-Rad1 clamp loader complex which is Dabigatran etexilate required for Chk1 activation after DNA damage. (healthdisparitiesks.org)
Structural basis for the subunit assembly of the anaphase-promoting complex. (ox.ac.uk)
The anaphase-promoting complex or cyclosome (APC/C) is an unusually large E3 ubiquitin ligase responsible for regulating defined cell cycle transitions. (ox.ac.uk)
The anaphase-promoting complex or cyclosome with the subunit Cdh1 (APC/C(Cdh1)) is an E3 ubiquitin ligase involved in the control of the cell cycle. (ox.ac.uk)
Cullin4
We analyzedthe architecture of the APC using a recently constructed budding yeaststrain that is viable in the absence of normally essential APC subunits.We found that the largest subunit, Apc1, serves as a scaffold thatassociates independently with two separable subcomplexes, one thatcontains Apc2 (Cullin), Apc11 (RING), and Doc1/Apc10, and another thatcontains the three TPR subunits (Cdc27, Cdc16, and Cdc23). (embl-heidelberg.de)
Apc4,Apc5, Cdc23, and Apc1 associate interdependently, such that loss of anyone subunit greatly reduces binding between the remaining three.Intriguingly, the cullin and TPR subunits both contribute to the bindingof Cdh1 to the APC. (embl-heidelberg.de)
Chen, HY & Chen, RH 2016, ' Cullin 3 ubiquitinligases in cancer biology: Functions and therapeutic implications ', Frontiers in Oncology , vol. 6, no. (tmu.edu.tw)
That is dependent on avoiding the NEDDylation from the Cullin-1 subunit from the ubiquitin ligase complicated E3-SCF-TrCP by exploiting the CSN5 deNEDDylase. (idplink.net)
Parkin1
This event relies on the coordinated and complementary activity of different ubiquitinligases, including PARKIN, SMURF1, and TRIM16. (bvsalud.org)
ATPase2
Structural characterization has revealed the presence of a dynein- like ATPase module and an unprecedented but poorly understood E3 module. (biorxiv.org)
In the cell, RNF213 was shown to be involved in fatty acid metabolism ( 11 ), and to associate with intracellular lipid droplets in a manner dependent on its E3 ligase and ATPase activities ( 12 ). (biorxiv.org)
Positive regulator2
As a positive regulator of plant immunity, E3 ligase SAUL1 is guarded by NLR protein SOC3. (ubc.ca)
The E3 molecule is responsible for binding the target protein substrate and transferring the ubiquitin from the E2 cysteine to a lysine residue on the target protein. (wikipedia.org)
Zinc finger1
Biochemical and activity-based probe analyses identify a non-canonical zinc finger domain as the E3 active site, which utilizes the strictly conserved Cys4462, not involved in zinc coordination, as the reactive nucleophile. (biorxiv.org)
Regulator2
Deletions of multiple GID subunits compromise cell proliferation, and this defect is accompanied by deregulation of critical cell cycle markers such as the retinoblastoma (Rb) tumor suppressor, phospho-Histone H3 and Cyclin A. We identify the negative regulator of pro-proliferative genes Hbp1 as a bonafide GID/CTLH proteolytic substrate. (elifesciences.org)
Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. (nature.com)
Cdc162
We found thatthe three TPR subunits display a sequential binding dependency, with Cdc27the most peripheral, Cdc23 the most internal, and Cdc16 between. (embl-heidelberg.de)
Three conserved tetratricopeptide repeat (TPR) subunits (Cdc16, Cdc23 and Cdc27) share related superhelical homo-dimeric architectures that assemble to generate a quasi-symmetrical structure. (ox.ac.uk)
Peptidase1
In this report we implicate a novel Dub ubiquitin-specific peptidase 20 (USP20) in the DDR by interacting with and regulating the protein level and function of Rad17. (healthdisparitiesks.org)
Cancers1
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
Cdh12
The E3 ligase APC/C(Cdh1) promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth. (ox.ac.uk)
Knocking down Cdh1 in melanoma cells in culture or before implantation in mice promoted doxorubicin resistance, whereas reexpressing wild-type Cdh1, but not E3 ligase-deficient Cdh1 or a mutant that could not interact with PAX3, restored doxorubicin sensitivity in melanoma cells both in culture and in xenografts. (ox.ac.uk)
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
Dependent1
Here, we demonstrate that RNF213 E3 activity is dependent on ATP binding, rather than ATP hydrolysis, and is particularly responsive to the ATP/ADP/AMP ratio. (biorxiv.org)
Activity1
We recently described the structure of M. musculus RNF213 (PDB: 6TAX) and characterized its enzymatic activity, revealing it as a large monomeric protein with a functional dynein-like AAA (ATPases Associated with diverse cellular Activities) core that exists alongside a novel E3 ligase module ( 16 ). (biorxiv.org)
Human1
RNF213/ALO17/mysterin (Ring Finger Protein 213) is the largest known human single-chain E3 ubiquitin ligase, first described as the major susceptibility factor for Moyamoya disease (MMD) ( 1 ), a disorder which causes aberrant vasculature development commonly leading to stroke and other complications ( 2 ). (biorxiv.org)
Genetic1
A snc1-influencing plant E3 ligase reverse (SNIPER) genetic screen identified two snc1-suppressors, SNIPER1 and SNIPER2, both of which completely suppress snc1-mediated autoimmunity upon overexpression. (ubc.ca)
Domain1
This entry represents a domain found in the C terminus of APC subunit 2. (embl-heidelberg.de)
Cell4
A particular cell usually contains only a few types of E1 molecule, a greater diversity of E2s, and a very large variety of E3s. (wikipedia.org)
In this study, we found that RING finger protein 4 (RNF4), a RING finger E3 ubiquitin ligase, is required for the RIPK1 autophosphorylation and subsequent cell death. (mdpi.com)
Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits (PubMed:23637203). (antikoerper-online.de)
Siah ubiquitinligases play important roles in a number of signaling pathways involved in the progression and spread of cancer in cell-based models, but their role in tumor progression remains controversial. (aacrjournals.org)
Important1
Ubiquitin is an important modifier in eukaryotic cells through many effects on the targeted protein. (helsinki.fi)